Nanovaccine could enhance cancer immunotherapy

NIBIB researchers have created a nanovaccine that could make a current approach to cancer immunotherapy more effective while also reducing side effects. The nanovaccine helps to efficiently deliver a unique DNA sequence to immune cells – a sequence derived from bacterial DNA and used to trigger an immune reaction. The nanovaccine also protects the DNA from being destroyed inside the body, where DNA-cutting enzymes are pervasive, as well as outside of the body when exposed to warm temperatures while being stored or transported. The researchers successfully tested the nanovaccine in mice and detailed their work in the March 2016 issue of the journal Nanoscale.

Tumors evade the immune system by suppressing its ability to recognize and kill cancer cells. The goal of immunotherapy is to normalize and harness the body’s immune system so that it can more effectively fight the Tumors.

Full story is available from NIBIB Website.

FDA Clears SPR Therapeutics Pain Management Device

SPR Therapeutics received clearance from the United States Food and Drug Administration to commercialize the SPRINT™ Peripheral Nerve Stimulation (PNS) System. SPRINT is the first and only completely reversible and minimallyinvasive peripheral nerve stimulation system cleared to provide relief of chronic and acute pain, including postoperative and posttraumatic pain.

“The FDA’s clearance comes at a critical time when physicians, patients and the U.S. healthcare system are seeking therapies to manage pain while reducing opioid use,” said Maria Bennett, SPR Therapeutics Founder, President and CEO. “SPR has developed a drugfree treatment for relieving chronic and acute pain. With more than 100 million Americans suffering from chronic pain, and more than two million people suffering severe acute and postoperative pain every year, we believe SPRINT will be a game changer in the world of pain management.”

The SPRINT PNS System includes a threadlike, coiled wire, or lead, and a matchboxsized wearable stimulator, about the weight of four quarters. The lead is placed percutaneously, or through the skin, via a fine needle and connects externally to the wearable stimulator. The stimulator delivers electrical stimulation through the lead, which activates peripheral nerves to achieve pain relief.

SPRINT is unique in that it allows lead placement as far as two to three centimeters from the targeted nerve. This simplifies the lead placement procedure for physicians and gives them the distinct ability to preferentially stimulate specific fibers of the nerve to maximize pain relief. This innovative approach to PNS is fully reversible, as the device is designed to be withdrawn without surgery at the end of the 30day treatment period.

A press release can be found from SPR Therapeutics website.

Simultaneous multiview capture and fusion improves spatial resolution in wide-field and light-sheet microscopy

Most fluorescence microscopes are inefficient, collecting only a small fraction of the emitted light at any instant. Besides wasting valuable signal, this inefficiency also reduces spatial resolution and causes imaging volumes to exhibit significant resolution anisotropy. We describe microscopic and computational techniques that address these problems by simultaneously capturing and subsequently fusing and deconvolving multiple specimen views. Unlike previous methods that serially capture multiple views, our approach improves spatial resolution without introducing any additional illumination dose or compromising temporal resolution relative to conventional imaging. When applying our methods to single-view wide-field or dual-view light-sheet microscopy, we achieve a twofold improvement in volumetric resolution (∼235  nm×235  nm×340  nm ) as demonstrated on a variety of samples including microtubules in Toxoplasma gondii, SpoVM in sporulating Bacillus subtilis, and multiple protein distributions and organelles in eukaryotic cells. In every case, spatial resolution is improved with no drawback by harnessing previously unused fluorescence.

Further information can be found from The Optical Society of America website.

Microswimmer Robots Can Work Together And Apart

Drexel University researchers, led by MinJun Kim, PhD, a professor in the College of Engineering, have successfully pulled off a feat that both sci-fi fans and Michael Phelps could appreciate. Using a rotating magnetic field they show how multiple chains of microscopic magnetic bead-based robots can link up to reach impressive speeds swimming through a liquid. Their finding is the latest step toward using the so-called “microswimmers” to deliver medicine and perform surgery inside the body.

In a paper recently published in Nature Scientific Reports, the mechanical engineers describe their process for magnetically linking and unlinking the beads while they’re swimming, and individually controlling the smaller decoupled robots in a magnetic field. This data helps further the concept of using microrobots for targeted, intravenous drug delivery, surgery and cancer treatment.

“We believe microswimmer robots could one day be used to carry out medical procedures and deliver more direct treatments to affected areas inside the body,” said U Kei Cheang, PhD, a postdoctoral research fellow in Drexel’s College of Engineering and an author of the paper. “They can be highly effective for these jobs because they’re able to navigate in many different biological environments, such as the blood stream and the microenvironment inside a tumor.”

One of the central findings is that longer chains can swim faster than shorter ones. This was determined by starting with a three-bead swimmer and progressively assembling longer ones. The longest chain examined by the group, 13-beads in length, reached a speed of 17.85 microns/second.

Drexel engineers have been adding to the understanding of microrobots for biomedical applications for nearly a decade, with the goal of producing a robotic chain that can travel inside the body, then decouple to deliver their medicinal payload or targeted treatment.

The reason for this approach is that a rather versatile robot that can do multiple tasks could be controlled using a single magnetic field.

The robot chains move by spinning, like a long screw-like propeller, in step with a rotating external magnetic field. So the faster the field rotates, the more the robots spin and the faster they move. This dynamic propulsion system is also the key to getting them to divide into shorter segments. At a certain rate of rotation the robotic chain will split into two smaller chains that can move independently of each other.

“To disassemble the microswimmer we simply increased the rotation frequency,” Cheang said. “For a seven-bead microswimmer, we showed that by upping the frequency 10-15 cycles the hydrodynamic stress on the swimmer physically deformed it by creating a twisting effect, which leads to disassembly into a three-bead and four-bead swimmer.”

Once they’re separated, the field can be adjusted to manipulate the three- and four-bead robots to move in different directions. Because the beads are magnetized, they can eventually be reconnected — simply by tweaking the field to bring them back into contact on the side with the corresponding magnetic charge. The team also determined optimal rotation rates and angle of approach to facilitate re-linking the microswimmer chains.

This finding is a key component of a larger project in which Drexel is partnering with 10 institutions of research and medicine from around the world to develop this technology for performing minimally invasive surgery on blocked arteries.

“For applications of drug delivery and minimally invasive surgery, future work remains to demonstrate the different assembled configurations can achieve navigation through various in vivo environments, and can be constructed to accomplish different tasks during operative procedures,” the authors write. “But we believe that the mechanistic insight into the assembly process we discussed in this research will greatly aid future efforts at developing configurations capable of achieving these crucial abilities.”

Full story can be found from Drexel University website.

New enzyme-mapping advance could help drug development

Scientists at MIT and the University of São Paulo in Brazil have identified the structure of an enzyme that could be a good target for drugs combatting three diseases common in the developing world.

The enzyme, fumarate hydratase (FH) is essential for metabolic processes of parasites that are responsible for the spread of three diseases: Leishmaniases, Chagas disease, and sleeping sickness. As such, understanding the enzyme’s structure could help researchers figure out how to inhibit FH enzymes, thereby providing new medical therapies.

“This enzyme is really critical for the metabolism of organisms like Leishmania major,” says Catherine Drennan, an MIT professor whose lab hosted the research. “If you knock it out, the organism should be dead.”

Leishmaniases are a group of diseases varying from severe skin ulcers to debilitation of internal organs, and are present in Asia, Africa, the Americas, and Southern Europe. Chagas disease, located mostly in Latin America, causes cardiac and intestinal complications, and can lead to heart failure. Sleeping sickness affects humans and other animals and is an often-deadly disease concentrated in Africa.

The study of FH began at the University of São Paulo, where researchers Patricia R. Feliciano and M. Cristina Nonato made important progress on studying Leishmania major FH. Feliciano then moved to MIT to complete the analysis of the enzyme structure with Drennan, a professor of chemistry and biology, and an investigator with the Howard Hughes Medical Institute.

“The exciting thing about this is thinking that my work could help people who have those diseases,” says Feliciano.

The paper, “Crystal structure of an Fe-S cluster-containing fumarate hydratase enzyme from Leishmania major reveals a unique protein fold,” is being published today in Proceedings of the National Academy of Sciences (PNAS). The authors are Feliciano, Drennan, and Nonato.

First in class

Fumarate hydratase enzymes fall into two types, class I and class II. The current study represents the first time that a class I fumarate hydratase enzyme has been mapped.

Significantly, the Leishmania major FH enzyme has a protein architecture — it vaguely resembles a human heart in appearance — that is distinctive from the structure of human fumurate hydratase.

“When we looked at the structure for the first time, it was like, ‘Whoa, it is completely different from the human FH enzyme,’” says Feliciano.

“The fact that it is a novel fold does add to the idea that this is a good drug target,” Drennan adds. “It has a lot of potential.”

Here’s why: The distinctive structure of class I FH makes it possible that drugs could target the parasite variant of the enzyme alone, while leaving intact the functionally equivalent enzymes that humans use.

“It’s an enzyme that does the exact same thing, but it’s a completely different enzyme,” Drennan explains. “That’s what makes this such an exciting target.”

Brazil connection

The finding stems from work Feliciano started doing nine years ago in Brazil in Nonato’s lab, but was not able to complete at the time, in part because of difficulties accessing the right equipment.

In 2012 Feliciano arrived at MIT, where the Drennan Lab has tools that let researchers form crystals of proteins under anaerobic (oxygen-free) conditions. Having formed a crystal of the Leishmania major FH enzyme, it still took Feliciano several months to completely map out the enzyme’s structure, partly because of its complexity, she notes.

Drennan emphasizes the complementary aspects of the research arrangement, with the research problem identified and important groundwork accomplished in Brazil, while MIT provided the right tools to solve the enzyme structure, and with the results hopefully having long-term application in Latin America and Africa.

“It’s a really lovely collaboration between the two groups and two countries,” Drennan says.

For that matter, Drennan says, the nature of globalization means diseases can spread worldwide in relatively short timespans these days. That means the need to find remedies for Leishmaniases, Chagas disease, and sleeping sickness is potentially global, too.

“I think it’s important to reflect on these health issues, and more people in the U.S. need to be aware of these diseases,” Drennan says. “The world is getting to be a smaller place.”

More information can be found from MIT website.

Good Attitudes About Aging Help Seniors Handle Stress

New research from North Carolina State University finds that having a positive attitude about aging makes older adults more resilient when faced with stressful situations.

“There has been a lot of research on how older adults respond to stress, but the findings have been mixed: some studies have found that older adults are less resilient than younger adults at responding to stress; some have found that they’re more resilient; and some have found no difference,” says Jennifer Bellingtier, a Ph.D. student at NC State and lead author of a paper describing the work. “We wanted to see whether attitudes toward aging could account for this disparity in research findings. In other words, are older adults with positive attitudes about aging more resilient than older adults with negative attitudes?”

The answer is yes.

For the study, researchers had 43 adults between the ages of 60 and 96 fill out a daily questionnaire for eight consecutive days. At the beginning of the study, participants were asked about their attitudes toward aging. For example, participants were asked if they felt they were as useful now as they had been when they were younger, and whether they were as happy as when they were younger.

The daily questionnaire asked participants about any stress they’d experienced that day, as well as the extent to which they experienced negative emotions, such as fear, irritability or distress.

The researchers also accounted for the personality of study participants. Were they optimistic and upbeat about everything, or are there benefits tied specifically to an individual’s attitudes about aging?

“We found that people in the study who had more positive attitudes toward aging were more resilient in response to stress – meaning that there wasn’t a significant increase in negative emotions,” Bellingtier says. “Meanwhile, study participants with more negative attitudes toward aging showed a sharp increase in negative emotional affect on stressful days.”

“This tells us that the way we think about aging has very real consequences for how we respond to difficult situations when we’re older,” says Shevaun Neupert, an associate professor of psychology at NC State and senior author on the paper. “That affects our quality of life and may also have health ramifications. For example, more adverse emotional responses to stress have been associated with increased cardiovascular health risks.”

“Our findings are likely applicable to other Americans, but it’s not clear to what extent the findings would be relevant elsewhere,” Bellingtier says. “Attitudes toward aging vary widely across cultures, and more work would need to be done to determine the importance of aging attitudes in other settings.”

The paper, “Negative aging attitudes predict greater reactivity to daily stressors in older adults,” will be published online at 8 a.m. on Aug. 3 in the Journal of Gerontology: Psychological Sciences. The work was done with funding from NC State.

Full story can be found from NCSU website.